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IRAK4 Gene Interleukin 1 Receptor Associated Kinase 4

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IRAK4 Gene Interleukin 1 Receptor Associated Kinase 4 IRAK4 gene interleukin 1 receptor associated kinase 4 Normal Function The IRAK4 gene provides instructions for making a protein that plays an important role in innate immunity, which is the body's early, nonspecific response to foreign invaders ( pathogens). The IRAK-4 protein is part of a signaling pathway that is involved in early recognition of pathogens and the initiation of inflammation to fight infection. In particular, the IRAK-4 protein relays signals from proteins called Toll-like receptors and IL-1 receptor-related proteins. As one of the first lines of defense against infection, Toll-like receptors recognize patterns that are common to many pathogens, rather than recognizing specific pathogens, and stimulate a quick immune response. The IL-1 receptor and related proteins recognize immune system proteins called cytokines that signal the need for an immune response. The resulting signaling pathway triggers inflammation, a nonspecific immune response that helps fight infection. Health Conditions Related to Genetic Changes IRAK-4 deficiency At least 20 mutations in the IRAK4 gene have been identified in people with IRAK-4 deficiency, an immune system disorder that leads to recurrent invasive bacterial infections. These gene mutations lead to an abnormally short, nonfunctional IRAK-4 protein or no protein at all. The loss of functional IRAK-4 protein blocks the initiation of inflammation in response to pathogens or cytokines that would normally help fight the infections. Because the early immune response is insufficient, bacterial infections occur often and become severe and invasive. Other Names for This Gene • interleukin-1 receptor-associated kinase 4 • IPD1 • IRAK-4 • IRAK4_HUMAN • NY-REN-64 • REN64 Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 1 A dditional Information & Resources Tests Listed in the Genetic Testing Registry • Tests of IRAK4 (https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=51135[geneid]) Scientific Articles on PubMed • PubMed (https://pubmed.ncbi.nlm.nih.gov/?term=%28%28IRAK4%5BTI%5D%29+ OR+%28interleukin-1+receptor-associated+kinase+4%5BTI%5D%29%29+AND+%2 8%28Genes%5BMH%5D%29+OR+%28Genetic+Phenomena%5BMH%5D%29%29 +AND+english%5Bla%5D+AND+human%5Bmh%5D+AND+%22last+3600+days%2 2%5Bdp%5D) Catalog of Genes and Diseases from OMIM • INTERLEUKIN 1 RECEPTOR-ASSOCIATED KINASE 4 (https://omim.org/entry/606 883) Research Resources • ClinVar (https://www.ncbi.nlm.nih.gov/clinvar?term=IRAK4[gene]) • NCBI Gene (https://www.ncbi.nlm.nih.gov/gene/51135) References • Li S, Strelow A, Fontana EJ, Wesche H. IRAK-4: a novel member of the IRAKfamily with the properties of an IRAK-kinase. Proc Natl Acad Sci U S A. 2002 Apr 16;99(8): 5567-72. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/11960013) or Free article on PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC122810/) • Medvedev AE, Lentschat A, Kuhns DB, Blanco JC, Salkowski C, Zhang S, Arditi M, Gallin JI, Vogel SN. Distinct mutations in IRAK-4 confer hyporesponsiveness tolipopolysaccharide and interleukin-1 in a patient with recurrent bacterialinfections. J Exp Med. 2003 Aug 18;198(4):521-31. Citation on PubMed (https://pubmed.ncbi.nl m.nih.gov/12925671) or Free article on PubMed Central (https://www.ncbi.nlm.nih.g ov/pmc/articles/PMC2194174/) • Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H, Al-Jumaah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR,Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A, Casanova JL. Pyogenic bacterial infections in humans with IRAK- 4deficiency. Science. 2003 Mar 28;299(5615):2076-9. Epub 2003 Mar 13. Citation on PubMed (https://pubmed.ncbi.nlm.nih.gov/12637671) • Suzuki N, Suzuki S, Yeh WC. IRAK-4 as the central TIR signaling mediator ininnate Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 2 immunity. Trends Immunol. 2002 Oct;23(10):503-6. Review. Citation on PubMed (htt ps://pubmed.ncbi.nlm.nih.gov/12297423) Genomic Location The IRAK4 gene is found on chromosome 12 (https://medlineplus.gov/genetics/chromos ome/12/). Page last updated on 18 August 2020 Page last reviewed: 1 November 2011 Reprinted from MedlinePlus Genetics (https://medlineplus.gov/genetics/) 3.
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